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In the July 2007 issue of the American Osteopathic Association's publication, AOA Health Watch, endocrinologist Jennifer Wojtowicz, DO, of the Cleveland Clinic Department of Endocrinology and Metabolism described how she diagnoses and treats prediabetes and the metabolic syndrome. Since that article appeared, there has been an increasing focus in the media and among health care professionals on America's “obesity epidemic,” metabolic syndrome, prediabetes, type 2 diabetes and cardiovascular risk.

The federal Centers for Disease Control and Prevention notes that about 57 million Americans have prediabetes and another 8% have full-blown diabetes mellitus. The CDC also estimates that about 30% to 40% of patients with prediabetes will develop type 2 diabetes within five years. Not only is prediabetes a precursor to type 2 diabetes, but it also raises the risk of developing both heart disease and stroke. The American Diabetes Association has responded by issuing new recommendations targeting these growing health problems and their increased CV risks. (See “new guidelines set,” page eS24).

In light of the increasing spotlight on obesity and prediabetes, we asked Dr. Wojtowicz to revisit her earlier account of how she diagnoses and treats such patients to find out if anything has changed since she expressed her considerations in the 2007 article, “Head it off at the pass: Understanding insulin resistance is key to diagnosing and treating prediabetes to prevent comorbidity.”

Dr. Wojtowicz said she still recommends lifestyle changes such as nutrition and exercise as the first line of treatment for metabolic syndrome and prediabetes, and she considers metformin the drug of choice, particularly for patients who don't do well on lifestyle interventions. She also occasionally prescribes rosiglitazone maleate or pioglitazone and considers prescribing medications that target the incretin system (ie exenatide and sitagliptin) relatively early in treatment since they do not cause weight gain. She explains that most diabetes treatments, such as rosiglitazone maleate and pioglitazone, are associated with weight gain. On the other hand, metformin does not cause weight gain.

According to Dr. Wojtowicz, “Virtually all physicians stress diet and exercise as first-line treatment when fasting glucose and glucose tolerance are impaired.” (See page eS25 for recent diagnostic guidelines for impaired fasting glucose and glucose tolerance).

Surgery an added option

Dr. Wojtowicz's approach hasn't changed much over the years, with one significant exception: She has since added another option to her treatment priorities—surgery, especially gastric bypass called Roux en-Y surgery or other bariatric surgery such as lap (gastric) band surgery and possibly sleeve gastrectomy.

“Gastric surgery has now become recognized in endocrinology as a cure for diabetes,” she says, giving as evidence that there is now a large body of literature favoring gastric bypass as treatment for diabetes patients. (For additional information, go to http://www.gastricbypass.com.)

Part of the rationale for bariatric surgery lies in the pervasiveness of obesity in the United States. According to recent CDC data published online in the Journal of the American Medical Association, not only are the vast majority of adults overweight, 34% are obese. In addition, 17% of children are obese. Even the youngest Americans are affected—10% of babies and toddlers are precariously heavy.

Dr. Wojtowicz explains that the heavier a person gets, the more joint problems he or she has, making it exceedingly painful to exercise. Consequently, that individual gains still more weight and exercise becomes even more difficult. “It's a vicious circle,” she points out, which can be turned around by gastric surgery to reduce weight and cure or prevent diabetes.

New guidelines set

The American Diabetes Association's “Current Guidelines for Pre-Diabetes,” from its position statement, “Standards of Medical Care in Diabetes revised in 2010.”

Tests for prediabetes

▪ FPG and OGTT

Both the Fasting Plasma Glucose [FPG*] test and the two-hour Oral Glucose Tolerance Test [OGTT**] are appropriate for prediabetes testing. The two-hour OGTT identifies people with either impaired fasting glucose or impaired glucose tolerance; therefore it picks up more prediabetic people at increased risk for the development of diabetes and cardiovascular disease than the FPG test. On the other hand, the two tests do not necessarily detect the same prediabetic individuals.

▪ Impaired fasting glucose (IFG)

A fasting glucose level between 100 and 125 mg/dL indicates (IFG).

▪ Impaired glucose tolerance (IGT)

A two-hour post-75-g glucose load/glucose concentration of between 140 to 199 mg/dL indicates, prediabetes both IFG and IGT fall into the official diagnosis of “prediabetes,” and both are risk factors for future diabetes.

▪ A1c

The ADA now promotes the use of the hemoglobin A1c (A1c) test to help reduce the number of undiagnosed patients and better identify people with prediabetes because that test is faster and easier than other diabetes tests.

▪ An A1c of 5.7 to 6.4 % suggests an increased risk for future diabetes, or prediabetes, and the cut-off point of 6.5 % and above indicates diabetes.

*The screening test of choice for diagnosing diabetes mellitus is the FPG test because it is simpler, more accurate, less expensive, and less variable than the two-hour OGTT, which is not necessary to diagnose diabetes and should rarely be used.

**The OGTT test may be useful however in patients with IFG to better define the risk of diabetes and CVD.

Treatment

▪ Lifestyle changes

Prediabetes is a major risk factor associated with metabolic syndrome. For patients with prediabetes, the goal is to decrease the risk of diabetes and cardiovascular disease by promoting physical activity and healthy food choices that result in moderate sustainable weight loss, or at a minimum, prevents further weight gain. Patients identified with prediabetes, should be tested and treated for other potential CVD risk factors.

▪ Medications

The ADA does not recommend drug therapy owing to the limited efficacy of treatment versus lifestyle modification, the potential for adverse drug reactions, and the lack of data supporting reduction of microvascular or macrovascular complications of diabetes in this patient population, as well as insufficient assessment of the cost-effectiveness of drug treatment.

Since not all patients are able to implement lifestyle modifications for various reasons, and based on limited data available, drug therapy may be a reasonable option to delay onset of type 2 diabetes and provide a cardiovascular benefit.

Source: American Diabetes Associaiton, “Standards of Medical Care in Diabetes-2010”.

Dr. Wojtowicz adds that an obese person who can barely walk because his or her knees are so bad is at higher risk of blood clots and bleeding during surgery. As a result, an orthopedic surgeon might tell such an individual to take off 40 pounds before surgery. “But how do you do this when you can't walk around the block?” She adds that “probably an overlooked risk of obesity and diabetes is joint problems.”

“As an endocrinologist, my approach is generally more aggressive than that of a family practitioner or internist,” Dr. Wojtowicz points out. She adds that she has been far more aggressive and for a longer time than most family physicians in recognizing and treating prediabetes and the metabolic syndrome.

Currently, there is an ongoing study at Cleveland Clinic—the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) study. In this trial, patients with type 2 diabetes are randomized to intense medical treatment or a surgical approach including gastric bypass or lap band surgery during a five-year study period. After surgery, many patients are able to go off their medications. However, the question that still needs to be answered is: How sustained will this be? Is the improvement purely because of weight loss or are there other changes? For more information, visit the Web site http://my.clevelandclinic.org/bariatric_surgery/research/stampede.aspx.

Clues to diagnosis

Dr. Wojtowicz identifies the metabolic syndrome both clinically and using well-established biochemical clues.

“I first look at my patients' body habitus, examining them to see if their waists are bigger than their hips, which indicates that there is fat around the organs. Intervisceral fat is the dangerous kind of fat, as opposed to subcutaneous fat. A person's build gives an important clue,” she explains.

Another clinical sign Dr. Wojtowicz looks for in early diabetes is skin changes, particularly acanthosis nigricans. This skin disorder is seen as velvety, light-brown-to-black markings usually on the neck, under the arms, or in the groin and is most often associated with obesity. Evidence shows that most patients with acanthosis nigricans have higher insulin levels than people weighing the same amount but who do not have such pigmentation.

In most cases, acanthosis nigricans is thought to be caused by elevated levels of insulin that activate insulin receptors in the skin forcing them to grow abnormally. Dieting or medications can reduce the circulating insulin, subsequently helping clear the skin. Insulin resistance may be caused by eating too much of the wrong foods, especially starches and sugars, resulting in elevated insulin levels.

Dr. Wojtowicz also relies on recommended blood tests, such as plasma glucose, oral glucose tolerance and total cholesterol. Triglycerides are especially important, she says; if they are high it might indicate prediabetes or metabolic syndrome. Her approach is to “look, test and treat aggressively to normalize cardiovascular risk factors.” She says that she agrees with her earlier assessment that “The sooner you treat, the fewer complications, and the easier it is to control” or prevent type 2 diabetes.

Emphasis remains the same

Dr. Wojtowicz's emphasis is much as it was in 2007. The root cause of type 2 diabetes is insulin resistance, and she uses the analogy of a hypothetical wheel with insulin resistance in the middle with spokes coming off it. Diabetes is one of these spokes, she says, and among the other spokes in this theoretical wheel of insulin resistance are hypertension, high cholesterol, sleep apnea and polycystic ovarian disease.

Dr. Wojtowicz says that she refers her early-diabetes and insulin-resistant patients to a nutritional counselor or a diabetic educator. She starts patients who do not respond to diet and exercise on medication as soon as possible.

This continuing medical education publication is supported by an educational grant from Merck & Co, Inc.